Intravenous lipid emulsions are used as a means of preventing or ameliorating essential fatty acid deficiency in patients who cannot tolerate oral intake. It is also used as a means of providing calories for patients who require parenteral nutrition instead of or as a supplement to oral feeding.
The commercially available sterile lipid emulsion compositions contain triglycerides derived from vegetable oils (neutral lipids) or other sources which represent 10 to 20% (weight/volume) of the lipid emulsions. The additional constituents of the sterile lipid emulsions include glycerin, and, as an emulsifying agent, either soy or egg phosphatides.
Egg yolk phosphatide which is purified in known manner, is the most commonly used emulsifier, although other emulsifiers are also used. These lipid emulsions are made by dispersing the egg yolk phosphatide in warm water using homogenization to create a fine dispersion to which the oil is added.
The conventional oil products used to supply the triglycerides are natural materials such as vegetable and like oils, including butter oil, coconut oil, canola oil, cottonseed oil, lard oil, olive oil, sesame seed oil, soya bean oil, and safflower oil. Soybean oil is preferred due to its ease of purification. These oils are readily accepted by mammals with little or no side effects, but they are primarily rich in fatty acids such as linoleic acid (C.sub.18:2) which is an omega-6 fatty acid. Linoleic acid is recognized to be an essential fatty acid and necessary for growth and development and the maintenance of normal cell function, since it is a primary constituent of cell membrane. Furthermore it is the precursor for arachidonic acid (C.sub.20:4) another essential fatty acid, which is the principal precursor for the dienoic prostaglandins, leukotrienes and other hydroperoxy-arachidonate derivatives.
It is known that fish oils are rich in C.sub.20-24 linear polyunsaturated acids having 5-7 double bonds, which are designated the omega-3 fatty acids. These include the fatty acids eicosapentaenoic acid (C.sub.20:5) and docosahexaenoic acid (C.sub.22:6). These acids are also precursors for trienoic prostaglandins and leukotrienes which have a different potency than their omega-6 (dienoic) equivalents. In addition, they are known to have some therapeutic value in treating heart disease, inflammatory disorders, and infection. However, providing large quantities of omega-3 and omega-6 fatty acids in the form of neutral lipids may not be the most optimal form to give to a stressed and/or malnourished patient, given the complexity of the metabolic processes necessary to process the artificial chylomicrons delivered in a sterile lipid emulsion. A more bioavailable form would be useful in treating these patients.
Thus it is desired to provide an improved sterile lipid emulsion that will provide calories and essential fatty acids from both the omega-3 and the omega-6 fatty acids, which, when provided in specific concentrations and combinations, will produce a pharmacological response elicited through the production of eicosanoids, including prostaglandins, leukotrienes and hydroperoxy-arichidonate derivatives.